Foresight Update 28

Page 4

Catalytic Structures

One of the natural applications of complex structures is
catalysis. The 3D placement of active sites is important in the
effective control of chemical reactions. In addition to its
importance as an application area, this is important to
nanotechnology as a source of new component parts, which may be
applied in either parallel or sequential techniques for
constructing new structures. The following three papers describe
advances in the application and analysis of catalytic structures.

Synthesis of porphyrins by
multi-enzyme, cell-free reactors

In the first paper, G. L. Verdine, writing in [Nature
(supp)384:11-13 7Nov96] describes the prospects for
natural product chemistry in modern drug design. Amongst other
developments, he describes the operation of a substantial enzyme
cascade, writing: "The ease with which such in vitro
biosynthetic reactions assemble complex organic molecules can be
truly remarkable: in one case, a cocktail of 12 enzymes converted
5-aminolevulinic acid to hydrogenobyrininc acid, an advanced
intermediate along the vitamin B12 biosynthetic pathway, giving a
20% overall yield. In a matter of hours, this bioreactor was able
to catalyse a 17-step conversion with an average stepwise yield
of 90%. ... As recently as ten years ago, the notion of
overproducing a dozen enzymes would have been greeted with
derision, but recent advances in polymerase chain
reaction-assisted overproduction systems and affinity tagging
technology have greatly reduced the investment of time and labor
necessary to obtain pure proteins in quantity." This
particular pathway is important to nanotechnologists because
porphyrins such as B12 are rigid, fused, ring systems,
potentially valuable as machine components. This application of
an enzyme system in a cell-free reactor also allows a wider
variety of potential substrates than in vivo techniques,
including substrates, intermediates, and products that would be
toxic to intact cells. The single vessel, multistep reactor is
also analogous to the mill systems described in Nanosystems,
albeit with diffusive transport.

X-ray diffraction pictures of
molecular motions

In the second paper, V. Srajer et. al., writing in [Science274:1726-1729 6Dec96], describe nanosecond x-ray
diffraction analysis of structural changes during photolysis of
the CO complex of myoglobin. They were able to measure shifts as
small as an "iron displacement of 0.32 Å from the heme
plane". They are currently able to measure events as early
as 4 nanoseconds after the laser dissociates the CO, but
anticipate that the "time resolution can be extended to the
100-ps domain if shorter laser pulses are used." At this
point the length of the x-ray pulses, which are currently 150 ps
long, will set the temporal resolution.

This technique will be very helpful in probing the sequence of
conformations important in the operation of molecular machines,
particularly when high flexibility may make unexpected structures
accessible, as in biopolymer systems. One feature detected in the
present study is a "transient docking site for the
photodissociated CO". In an analogous system designed for
high speed operation, this might represent a detection of an
unexpected speed limiting temporary trap, which is only visible
in these transient structures. While this technique sees
intermediate structures in a reaction, it is not generally fast
enough to probe the potential energy surface in the neighborhood
of unstable transition states themselves, where timescales are
typically 0.1 ps. Those time scales are accessible to purely
optical techniques, however this x-ray technique provides much
more spatial information. One limitation of this paper's
technique is that it sees an average of the structures produced
by a reaction, so too many accessible reaction pathways can
average away useful information.

Catalytic DNA and combinatorial
chemistry

In the third paper, R. Rawls, writing in [C&EN75:33-35
3Feb97], describes work by a number of labs on catalytic DNA.
Rawls writes that "DNA is an ideal molecule to investigate
using combinational chemistry" and all of the labs involved
have used combinational techniques to select their catalysts. The
reactions catalyzed have included RNA cleavage, DNA cleavage, DNA
ligation, and metal insertion into porphyrins. The DNA catalysts
have been much smaller than comparable protein catalysts. For
example, D. Sen's DNA for porphyrin metallation "has a
molecular weight of roughly 8,000" while a mammalian protein
that catalyzes the same reaction has a weight of around 42,000.
Since these catalysts are DNA, they may be relatively simple to
incorporate into 3D DNA frameworks, such as those that N.
Seeman has developed, allowing 3D placement of several
catalytic sites. In addition, the small size of the DNA catalysts
may allow the same function to be contained in a smaller volume
than would be required for protein catalysts.

One technique that is expected to become important in
nanotechnology is mechanochemistry, the process of directing
chemical reactions by mechanical forces on the reactants. The
following paper describes experimental work in this area.

An AFM experiment by S. P. Jarvis et. al [Nature384:
247-249 21Nov96] succeeded in tracing the force curve of an Si/Si
tip/substrate pair smoothly through the negative stiffness
regime. They augmented the force feedback of their lever with a
magnetic feedback loop to increase the effective d.c. stiffness
to 37 N/m. They measured the force curve by slightly perturbing
the force at a frequency above the response of the feedback loop
but below the free resonance frequency of their AFM lever,
measuring the displacement (and hence the effective stiffness of
the tip/sample interaction). They integrated the stiffness to
yield the force curve, and integrated the force curve to yield
the effective potential, finding "the energy point of
inflection is at 2.5 eV, and that the maximum (tensile) force is
just under 0.3 nN, not impossibly far from the expected ~1.5 nN
for a single Si-Si bond, and rather larger than expected for a
purely Van der Waals bond." They found almost no hysteresis
in their force curve with feedback turned on, "observing a
conservative potential interaction." This is experimental
evidence for thermodynamically reversible mechanochemistry, in a
silicon analog of the sp3 carbon bond cleavage case
analyzed in section 8.5.3 of Drexler's Nanosystems.

Jeffrey Soreff is a researcher at IBM with an interest in
nanotechnology

Media
Watch

General circulation media have given much attention to the
prospects of nanotechnology in recent months, mostly favorably
and accurately. The principal exception is a publication that
usually does better, the New York Times.

Newsweek
Magazine's January 27, 1997, cover story took a peek into the
next millennium, and found nanotechnology a likely part of the
future. In the section devoted to science, "Uncovering
Secrets, Big and Small," science writer Sharon Begley
started by describing DNA-related advances such as "gene
pharming" that seem "certain to occur." She then
turned immediately to the prospects of nanotechnology:

"Wilder forecasts have stiffer odds. Will the 21st
century see nano-assemblers? These microrobots would break
down the chemical bonds of cheap ingredients - grass and
water, say-- and reassemble the carbon, nitrogen, hydrogen
and other molecules into, for instance, a sirloin steak. You
scoff? It is not much more incredible than a cow's ability to
do the same. And scanning tunneling microscopes can already
manipulate single atoms, which is what the assemblers would
do."

Concluding the three-page article, Begley returns to the
promise of nanotechnology:

"Dudley
Herschbach of Harvard University foresees making
molecules that self-assemble and self-replicate, sometime in
the next 35 years. Biochemists are close to doing it. And
they have a good idea of what to do with those creations:
make those grass-into-sirloin nano-assemblers. In 1997 that
seems like so much science fiction, while genetic
discoveries, for instance, seem like sure bets. But
sometimes, in science, the dark horse comes in before the
favorite."

"Nanotechnologists drawing on advances in engineering,
biotechnology and computer science want to use individual atoms
as if they were Tinkertoys to create new materials and products
that in some cases-- like those fictional self-constructed
buildings-- could mimic living organisms, reproduce, and even
assemble still other objects when turned loose by the
trillions," Kanaley wrote.

Smalley is quoted as describing molecular nanotechnology as
"a very broad field and in many ways, the ultimate
playground." Futurist Arthur Shostak of Drexel University is
quoted discussing the major social and economic upheaval if
nanotechnology succeeds in extending life span or in replicating
raw materials, or food. "Nano threatens the entire
production infrastructure that you and I take for granted,"
he said.

Merkle is quoted on the notion of self-replication
as the basis for nanotechnology. "Potatoes don't cost very
much, even though they are miracles of biology with tens of
thousands of genes and proteins. The reason they are inexpensive
is that a potato can make more potatoes," he said.

Technical Review, a
publication of the Massachusetts Institute of Technology,
featured a major article by Ralph Merkle, "It's
a Small, Small, Small, Small World," in which he laid
out the concepts of nanotechnology and the current state of the
field. "Natural diamond is expensive, we can't make it in
the shapes we want, and it shatters. Nanotechnology will let us
inexpensively make shatterproof diamond (with a structure that
might resemble diamond fibers) in exactly the shapes we want.
This would let us make a Boeing 747 that would weight
one-fiftieth of today's version without any sacrifice in
strength," Merkle wrote. Merkle has placed an expanded
version of his article on his Web site.

Scientific American's
February 1997 issue included a half-page article under the
heading "Nanotechnology: Scoring with Buckyballs."
Writer Erica Garcia discussed Dr. Smalley's use of
fullerene tubes into scanning-force microscope (SFM) probes,
noting their durability against "crashes" because of
inherent flexibility. The same article pictured and discussed a molecular-sized
abacus created at IBM Zurich Research Laboratory by Dr. James
Gimzewski (a scheduled speaker at this fall's Foresight Conference on
Molecular Nanotechnology). His prototype calculator lines up
buckyballs on a grooved copper plate, allowing abacus-like
manipulation of the molecular "beads" with a scanning
tunneling microscope (STM). He's quoted as noting that this is
the scale equivalent of "operating a standard abacus with
the Eiffel Tower," but the story notes that "by showing
what is possible, buckyballs are starting to score big in the
small field of nanotechnology."

Muddled identity permeated a New
York Times article in January that not only mistakenly
identified micro-electromechanical systems (MEMS) as the
equivalent of nanotechnology, but also misidentified the creator
of the concept as "Eric Drexel", and wrongly asserted
that "the field of nanotechnology, practically speaking, has
not done much since the late physicist Richard
Feynman laid out its plans." Eh? Didn't the Times
cover Smalley's
Nobel Prize for work in nanotechnology? The article is more a
discussion about science fiction (Gibson's Idoru and
Stephenson's Diamond Age) than science. It's definitely
not worth searching out.

Man clones sheep. Man clones monkeys.
What's next, an army of super-warriors? The near-hysterical
reactions within media and government circles to these
developments offers one potential scenario for considering the
reverberations that could occur when nanotechnology is realized.
Self-proclaimed experts weighed in with lofty opinions, many of
which misrepresented the science, the ethical issues, or both. TheEconomist summarized the media
reaction well:

"The news of Dolly hit the headlines with a sickening
thud-- the sound of a sheep that had been launched at full
speed at the world's pundits. And the pundits did not
disappoint. Their responses were dismissive, scared, funny,
outrageous, wise and stupid by turns. The important thing, it
seemed, was to think of something to say, and say it first.
Journalists, hungry for copy, swallowed their quotes and
spread them on the page, in between invoking Aldous Huxley's
'Brave New World' and Ira Levin's 'The Boys from Brazil'--
apparently the only literary references to cloning anyone
could remember....President Clinton, meanwhile, had only to
say that there were 'serious ethical questions' to generate
gravitas. One of the advantages of being president is that no
one has the termerity to ask you too closely what the
questions are."

Newsweek's Sharon Begley (see above) also offered
a thoughtful discussion of the ethical and science issues, but
concluded with a blunt assessment:

"If Dolly's creation offers any lessons, it is these.
First, that which is not absolutely prohibited by the laws of
nature is possible. Second, science, for better or worse,
almost always wins; ethical qualms may throw some roadblocks
in its path, or affect how widespread a technique becomes,
but rarely is moral queasiness a match for the onslaught of
science."

One positive aspect of the debate over human cloning is that
it creates yet another difficult mixture of science and ethics
that will give society practice in dealing with such fusions
prior to having to come to grips with the potentially
controversial applications of nanotechnology.